Phenotypes associated with this allele

• Allele Symbol: Upp1^tm1Gp
• Allele Name: targeted mutation 1, Giuseppe Pizzorno
• Allele ID: MGI:3586525
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Upp1^tm1Gp/Upp1^tm1Gp	involves: 129	MGI:3587637
cx2	Tymp^tm1Mihi/Tymp^tm1Mihi Upp1^tm1Gp/Upp1^tm1Gp	involves: 129 * 129X1/SvJ * C57BL/6J	MGI:3830854

Genotype
MGI:3587637

hm1

• Allelic Composition: Upp1^tm1Gp/Upp1^tm1Gp
• Genetic Background: involves: 129

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

homeostasis/metabolism

abnormal blood homeostasis ( J:99912 )

• increased uridine concentration: 6 times higher in plasma

abnormal enzyme/coenzyme level ( J:99912 )

abnormal urine nucleoside level ( J:99912 )

• increased uridine concentration: 24 times higher in urine

abnormal enzyme/coenzyme activity ( J:99912 )

abnormal nucleotide metabolism ( J:99912 )

• increased uridine concentration: 6 times higher in plasma, 5-6 times higher in lung and gut; 2-3 times higher in liver and kidney

decreased physiological sensitivity to xenobiotic ( J:99912 )

• decreased sensitivity to 5-fluorouracil

renal/urinary system

abnormal urine nucleoside level ( J:99912 )

• increased uridine concentration: 24 times higher in urine

behavior/neurological

impaired behavioral response to xenobiotic ( J:99912 )

• decreased sensitivity pentobarbital induced loss of righting reflex

Genotype
MGI:3830854

cx2

• Allelic Composition: Tymp^tm1Mihi/Tymp^tm1Mihi; Upp1^tm1Gp/Upp1^tm1Gp
• Genetic Background: involves: 129 * 129X1/SvJ * C57BL/6J

nervous system

abnormal brain white matter morphology ( J:144245 )

• brain white matter contains multiple vacuoles in the subcortical, periventricular, internal capsule and cerebellar white matter unlike in wild-type mice

• vacuoles are larger and more abundant in the cerebellum

• at 22 months, mice exhibit an increase in T2 signal on an MRI in the cerebral white matter, an indication of leukoencephalopathy

abnormal basal ganglion morphology ( J:144245 )

• older mice exhibit vacuoles in the basal ganglia unlike in wild-type mice

abnormal cerebellum dentate nucleus morphology ( J:144245 )

• older mice exhibit vacuoles in the dentate nuclei unlike in wild-type mice

brain vacuoles ( J:144245 )

• brain white matter contains multiple vacuoles in the subcortical, periventricular, internal capsule and cerebellar white matter unlike in wild-type mice

cellular

abnormal mitochondrial morphology ( J:144245 )

• mitochondrial DNA in the brain is reduced 27% compared to in wild-type mice

• depletion of mtDNA is more severe in older mice

abnormal mitochondrial ATP synthesis coupled electron transport ( J:144245 )

• the mitochondrial respiratory chain is deficient in the brain with 30% less complex I and IV activities compared to in wild-type mice

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:144245 )

• thymidine phosphorylase activity is decreased in the liver and undetectable in the brain, heart, lung, muscle, spleen, small intestine, and kidney unlike in wild-type mice

abnormal nucleotide metabolism ( J:144245 )

• mice exhibit an increase in thymidine and deoxyuridine in the brain, lung, spleen, kidney, heart, muscle, small intestine and liver compared to in wild-type mice

• mitochondrial nucleotide pools in the liver and brain are unbalanced with increased deoxythymidine triphosphate in both organs and increased deoxycytidine triphosphate in the brain compared to in wild-type mice

skeleton

kyphosis ( J:144245 )

• at 5 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mitochondrial DNA depletion syndrome 1		DOID:0080119	OMIM:603041	J:144245